Can you take azithromycin and doxycycline together for chlamydia

Summary

Background

Anorectal infections with Chlamydia trachomatis are commonly found in women. Although the efficacy of doxycycline and azithromycin is comparable in the treatment of urogenital infection, their efficacies toward anorectal infection remain unclear. We therefore aimed to compare a single dose of azithromycin with a 7-day course of doxycycline for the treatment of anorectal C trachomatis infection in women with concurrent vaginal infection.

Methods

We did a multicentre, open-label, randomised, controlled, superiority trial involving four sexually transmitted infection screening centres and three pregnancy termination centres in France. We included sexually active adult women (≥18 years) with a positive C trachomatis vaginal swab who agreed to provide self-collected anorectal swabs for C trachomatis detection. Participants were randomly assigned (1:1), using block sizes of six and eight and stratification by each investigating centre, to orally receive either azithromycin (a single 1-g dose, with or without food) or doxycycline (100 mg in the morning and evening at mealtimes for 7 days [ie, 100 mg of doxycycline twice per day for 7 days]). All laboratory staff who did the bacteriological analyses, but not the participants and the investigators, were masked to the treatment groups. The primary outcome was the microbiological anorectal cure rate defined as a C trachomatis-negative nucleic acid amplification test (NAAT) result in anorectal specimens 6 weeks after treatment initiation among women who had a baseline C trachomatis-positive anorectal NAAT result. The primary analysis was done in the modified intention-to-treat population, with multiple imputation, which included all women who underwent randomisation and had a C trachomatis-positive vaginal and anorectal NAAT result at baseline. Adverse events were reported in all women who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT03532464.

Findings

Between Oct 19, 2018, and April 17, 2020, we randomly assigned a total of 460 participants to either the doxycycline group (n=230) or the azithromycin group (n=230). Four (1%) of 460 participants were excluded because they refused to take doxycycline or were found to be ineligible after randomisation. Among the 456 participants, 357 (78%) had a concurrent C trachomatis-positive anorectal NAAT result at baseline; 184 (52%) of 357 were in the doxycycline group and 173 (48%) were in the azithromycin group (ie, the modified intention-to-treat population). Microbiological anorectal cure occurred in 147 (94%) of 156 participants in the doxycycline group (28 missing values) versus 120 (85%) of 142 in the azithromycin group (31 missing values; adjusted odds ratio with imputation of missing values 0·43 [95% CI 0·21–0·91]; p=0·0274). Reported adverse events possibly related to treatment were notified in 53 (12%) of 456 women: 24 (11%) of 228 in the doxycycline group and 29 (13%) of 228 in the azithromycin group. Gastrointestinal disorders were the most frequently occurring, in 43 (9%) of 456 women: 17 (8%) of 228 in the doxycycline group and 26 (11%) of 228 in the azithromycin group.

Interpretation

The microbiological anorectal cure rate was significantly lower among women who received a single dose of azithromycin than among those who received a 1-week course of doxycycline. This finding suggests that doxycycline should be the first-line therapy for C trachomatis infection in women.

Funding

French Ministry of Health.

Translation

For the French translation of the abstract see Supplementary Materials section.

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References

  1. 1.
    • Rowley J
    • Vander Hoorn S
    • Korenromp E
    • et al.

    Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016.

    Bull World Health Organ. 2019; 97 (): 548
  2. 2.
    • Goulet V
    • de Barbeyrac B
    • Raherison S
    • Prudhomme M
    • Semaille C
    • Warszawski J

    Prevalence of Chlamydia trachomatis: results from the first national population-based survey in France.

    Sex Trans Infect. 2010; 86: 263-270
  3. 3.
    • Kersaudy-Rahib D
    • Lydie N
    • Leroy C
    • et al.

    Chlamyweb Study II: a randomised controlled trial (RCT) of an online offer of home-based Chlamydia trachomatis sampling in France.

    Sex Trans Infect. 2017; 93: 188-195
  4. 4.
    • Peuchant O
    • de Diego S
    • Le Roy C
    • et al.

    Comparison of three real-time PCR assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in young pregnant women.

    Diagn Microbiol Infect Dis. 2015; 83: 335-337
  5. 5.
    • Toyer AL
    • Trignol-Viguier N
    • Mereghetti L
    • et al.

    Interest of simultaneous Chlamydia trachomatis and Neisseria gonorrhoeae screening at the time of preabortion consultation.

    Contraception. 2012; 86: 572-576
  6. 6.
    • Andersson N
    • Boman J
    • Nylander E

    Rectal chlamydia—should screening be recommended in women?.

    Int J STD AIDS. 2017; 28: 476-479
  7. 7.
    • Chandra NL
    • Broad C
    • Folkard K
    • et al.

    Detection of Chlamydia trachomatis in rectal specimens in women and its association with anal intercourse: a systematic review and meta-analysis.

    Sex Trans Infect. 2018; 94: 320-326
  8. 8.
    • Ding A
    • Challenor R

    Rectal chlamydia in heterosexual women: more questions than answers.

    Int J STD AIDS. 2014; 25: 587-592
  9. 9.
    • Sethupathi M
    • Blackwell A
    • Davies H

    Rectal Chlamydia trachomatis infection in women. Is it overlooked?.

    Int J STD AIDS. 2010; 21: 93-95
  10. 10.
    • Rank RG
    • Yeruva L

    Hidden in plain sight: chlamydial gastrointestinal infection and its relevance to persistence in human genital infection.

    Infect Immun. 2014; 82: 1362-1371
  11. 11.
    • Lanjouw E
    • Ouburg S
    • de Vries HJ
    • Stary A
    • Radcliffe K
    • Unemo M

    2015 European guideline on the management of Chlamydia trachomatis infections.

    Int J STD AIDS. 2016; 27: 333-348
  12. 12.
    • Kong FY
    • Tabrizi SN
    • Law M
    • et al.

    Azithromycin versus doxycycline for the treatment of genital chlamydia infection: a meta-analysis of randomized controlled trials.

    Clin Infect Dis. 2014; 59: 193-205
  13. 13.
    • Kong FY
    • Tabrizi SN
    • Fairley CK
    • et al.

    The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis.

    J Antimicrob Chemother. 2015; 70: 1290-1297
  14. 14.
    • Chen LF
    • Wang TC
    • Chen FL
    • et al.

    Efficacy of doxycycline versus azithromycin for the treatment of rectal chlamydia: a systematic review and meta-analysis.

    J Antimicrob Chemother. 2021; 76: 3103-3110
  15. 15.
    • Peuchant O
    • Lhomme E
    • Kret M
    • et al.

    Randomized, open-label, multicenter study of azithromycin compared with doxycycline for treating anorectal Chlamydia trachomatis infection concomitant to a vaginal infection (CHLAZIDOXY study).

    Medicine. 2019; 98e14572
  16. 16.
    • Haute Autorité de Santé

    Réévaluation de la stratégie de dépistage des infections à Chlamydia trachomatis.

  17. 17.
    • Rodriguez P
    • de Barbeyrac B
    • Persson K
    • Dutilh B
    • Bébéar C

    Evaluation of molecular typing for epidemiological study of Chlamydia trachomatis genital infections.

    J Clin Microbiol. 1993; 31: 2238-2240
  18. 18.
    • Stevens MP
    • Twin J
    • Fairley CK
    • et al.

    Development and evaluation of an ompA quantitative real-time PCR assay for Chlamydia trachomatis serovar determination.

    J Clin Microbiol. 2010; 48: 2060-2065
  19. 19.
    • Dombrowski JC
    • Wierzbicki MR
    • Newman LM
    • et al.

    Doxycycline versus azithromycin for the treatment of rectal chlamydia in men who have sex with men: a randomized controlled trial.

    Clin Infect Dis. 2021; 73: 824-831
  20. 20.
    • Dukers-Muijrers N
    • Wolffs PFG
    • De Vries H
    • et al.

    Treatment effectiveness of azithromycin and doxycycline in uncomplicated rectal and vaginal Chlamydia trachomatis infections in women: a multicenter observational study (FemCure).

    Clin Infect Dis. 2019; 69: 1946-1954
  21. 21.
    • Lau A
    • Kong FYS
    • Fairley CK
    • et al.

    Azithromycin or doxycycline for asymptomatic rectal Chlamydia trachomatis.

    N Engl J Med. 2021; 384: 2418-2427
  22. 22.
    • Khosropour CM
    • Soge OO
    • Suchland R
    • et al.

    Recurrent/intermittent vaginal and rectal chlamydial infection following treatment: a prospective cohort study among female sexually transmitted disease clinic patients.

    J Infect Dis. 2019; 220: 476-483
  23. 23.
    • Heijne JCM
    • van Liere G
    • Hoebe C
    • Bogaards JA
    • van Benthem BHB
    • Dukers-Muijrers N

    What explains anorectal chlamydia infection in women? Implications of a mathematical model for test and treatment strategies.

    Sex Trans Infect. 2017; 93: 270-275
  24. 24.
    • Rank RG
    • Yeruva L

    An alternative scenario to explain rectal positivity in chlamydia-infected individuals.

    Clin Infect Dis. 2015; 60: 1585-1586
  25. 25.
    • Leenen J
    • van Liere G
    • Hoebe C
    • Hogewoning AA
    • de Vries HJC
    • Dukers-Muijrers N

    A longitudinal study to investigate previous Chlamydia trachomatis infection as a risk factor for subsequent anorectal infection in men who have sex with men (MSM) and women visiting STI clinics in the Netherlands.

    Epidemiol Infect. 2019; 147: e214
  26. 26.
    • Dukers-Muijrers N
    • Wolffs PFG
    • de Vries HJC
    • Gotz HM
    • Janssen K
    • Hoebe C

    Viable bacterial load is key to azithromycin treatment failure in rectally Chlamydia trachomatis infected women (FemCure).

    J Infect Dis. 2019; 220: 1389-1390
  27. 27.
    • Kong FY
    • Tabrizi SN
    • Fairley CK
    • et al.

    Higher organism load associated with failure of azithromycin to treat rectal chlamydia.

    Epidemiol Infect. 2016; 144: 2587-2596
  28. 28.
    • Janssen KJ
    • Hoebe CJ
    • Dukers-Muijrers NH
    • Eppings L
    • Lucchesi M
    • Wolffs PF

    Viability-PCR shows that NAAT detects a high proportion of DNA from non-viable Chlamydia trachomatis.

    PLoS One. 2016; 11e0165920
  29. 29.
    • Dragovic B
    • Nwokolo N

    Update on the treatment of Chlamydia trachomatis (CT) infection.

    BASHH Clinical Effectiveness group, 2018
  30. 30.
    • Workowski KA
    • Bachmann LH
    • Chan PA
    • et al.

    Sexually transmitted infections treatment guidelines, 2021. Centers for Disease Control and Prevention.

    MMWR Recomm Rep. 2021; 70: 1-187

Article Info

Publication History

Identification

DOI: https://doi.org/10.1016/S1473-3099(22)00148-7

Copyright

© 2022 Elsevier Ltd. All rights reserved.

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Linked Articles

  • Doxycycline: the universal treatment for anogenital chlamydia
    • The results of the randomised trial in The Lancet Infectious Diseases by Olivia Peuchant and colleagues are welcomed and should come as no surprise.1 After all, doxycycline is known to be more efficacious than azithromycin for the treatment of rectal chlamydia in men,2 and randomised data from Peuchant and colleagues' study now confirm the same is true for women. However, the issue in women is slightly more intriguing, given around two-thirds of the women had not had anal sex and rectal infection was thought to come mainly from contamination or autoinoculation from the genital tract.

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Which is better for chlamydia doxycycline or azithromycin?

Background: Azithromycin and doxycycline are both recommended treatments for rectal Chlamydia trachomatis (CT) infection, but observational studies suggest that doxycycline may be more effective.

Can I take doxycycline and Zpack at same time?

Interactions between your drugs No interactions were found between Azithromycin Dose Pack and doxycycline. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.

Which is stronger doxycycline or azithromycin?

Conclusion: Azithromycin and doxycycline are equally efficacious in achieving microbial cure and have similar tolerability. Further head-to-head trials comparing these antibiotics are unnecessary.

How long until doxycycline clears chlamydia?

It takes 7 days for the medicine to work in your body and cure Chlamydia infection. If you have sex without a condom during the 7 days after taking the medicine, you could still pass the infection to your sex partners, even if you have no symptoms.